Disturbances in maternal care have been associated with impairments in affective and cognitive development of the offspring. In humans, there is growing evidence that postpartum mood disorders have a negative impact on the mother-child relationship, and the child's social, emotional, and cognitive development. Genetic, hormonal, and environmental influences are believed to play a role in the development of depressive and anxiety disorders, particularly in the post-partum period. Understanding the neurobiological factor(s) that may predispose to postpartum mood disorders and affect maternal behavior, as well as the factors that may be protective are therefore, of high clinical significance. We have recently developed a transgenic mouse model that over-expresses the serotonin 1a (5-HT1a) receptor in hippocampus. Our preliminary data show that transgenic female mice: 1) exhibit significant impairments in maternal behavior in the post-partum period;2) this impairment in maternal behavior is associated with increases in anxiety-like behavior;3) the anxiety-like behavior is limited to the post-partum period. Non-pregnant virgin females do not exhibit any anxiety-like or depressive-like behaviors;4) the impairments in maternal behavior are prevented if the male partner is kept with the female during the pre-partum and post-partum period. This exploratory/developmental R21 application seeks to: 1) further investigate the post-partum behavioral phenotype of these animals (Specific Aim 1), 2) begin to characterize some of the neurochemical changes that may be associated with impaired maternal behavior, and with the "protective" effect of the partner in this model (Specific Aim 2). The results will serve as a foundation for future studies investigating the mechanisms whereby 5-HT1a overexpression influences maternal behavior, and how social bonding buffers the behavioral impact of this genetic alteration. It is hoped that this animal model will be a useful tool in understanding the specific gene-environment interactions that may influence the development of post-partum mood and anxiety disorders, and may modulate the expression of maternal care. As such, this application is consistent with the goals of PA-06-334. PUBLIC HEALTH RELEVANCE: Disturbances in maternal care have been associated with impairments in the affective and cognitive development of the offspring. This application seeks to investigate the role of a specific serotonin molecule, the serotonin 1a receptor, on maternal behavior, using a mouse model that over-expresses serotonin 1a in brain. It is hoped that this animal model will be a useful tool in understanding the specific gene-environment interactions that modulate the expression of maternal care.